The CYP19 RS4646 Polymorphism IS Related to the Prognosis of Stage I–II and Operable Stage III Breast Cancer

Purpose

Aromatase, encoded by the CYP19 gene, catalyzes the final step of the conversion of androgens to estrogens. Given the critical role of CYP19 in estrogen synthesis, the potential influence of CYP19 rs4646 polymorphism on breast cancer survival, deserves further study.

Methods

Genotyping for CYP19 rs4646 variants was performed on 406 Chinese women with stage I–II and operable stage III breast cancer. Associations were evaluated between CYP19 rs4646 genotypes and disease-free survival (DFS).

Results

In premenopausal patients, women who are homozygous for the minor allele (AA) have a longer DFS compared with those carrying the major allele (CC or AC) (87 months versus 48.7 months; Hazard ratio (HR) = 0.56, 95 % CI = 0.318-0.985, P = 0.041). These differences were further demonstrated by a multivariate analysis (HR = 0.456, 95 % CI = 0.249-0.836, P = 0.011). Conversely, the same variant (AA) was estimated to be associated with a poorer DFS in postmenopausal women (AA versus AC or CC: 13.7 months versus 56.3 months; HR = 2.758, 95 % CI = 1.432-5.313, P = 0.002). Furthermore, the differences were confirmed by the COX proportional hazards model (HR = 2.983, 95% CI =1.494-5.955, P = 0.002).

Conclusions

The present study indicates that CYP19 rs4646 polymorphism is related to DFS in early breast cancer and that the prognosis index of the homozygous for the minor allele (AA) may depend on menopause status. The findings are novel, if confirmed, rs4646 genotypes may provide useful information for routine management in breast cancer.     

Effective Chemoimmunotherapy with Anti-TGFβ Antibody and Cyclophosphamide in a Mouse Model of Breast Cancer

TGFβ is reportedly responsible for accumulation of CD4⁺Foxp3⁺ regulatory T cells (Tregs) in tumor. Thus, we treated mouse 4T1 mammary carcinoma with 1D11, a neutralizing anti-TGFβ (1,2,3) antibody. The treatment delayed tumor growth, but unexpectedly increased the proportion of Tregs in tumor. In vitro, 1D11 enhanced while TGFβ potently inhibited the proliferation of Tregs. To enhance the anti-tumor effects, 1D11 was administered with cyclophosphamide which was reported to eliminate intratumoral Tregs. This combination resulted in long term tumor-free survival of up to 80% of mice, and the tumor-free mice were more resistant to re-challenge with tumor. To examine the phenotype of tumor infiltrating immune cells, 4T1-tumor bearing mice were treated with 1D11 and a lower dose of cyclophosphamide. This treatment markedly inhibited tumor growth, and was accompanied by massive infiltration of IFNγ-producing T cells. Furthermore, this combination markedly decreased the number of splenic CD11b⁺Gr1⁺ cells, and increased their expression levels of MHC II and CD80. In a spontaneous 4T1 lung metastasis model with resection of primary tumor, this combination therapy markedly increased the survival of mice, indicating it was effective in reducing lethal metastasis burden. Taken together, our data show that anti-TGFβ antibody and cyclophosphamide represents an effective chemoimmunotherapeutic combination.     

Gene Expression of the EGF System—a Prognostic Model in Non–Small Cell Lung Cancer Patients Without Activating EGFR Mutations

OBJECTIVES: Contradicting results have been demonstrated for the expression of the epidermal growth factor receptor (EGFR) as a prognostic marker in non–small cell lung cancer (NSCLC). The complexity of the EGF system with four interacting receptors and more than a dozen activating ligands is a likely explanation. The aim of this study is to demonstrate that the combined network of receptors and ligands from the EGF system is a prognostic marker. MATERIAL AND METHODS: Gene expression of the receptors EGFR, HER2, HER3, HER4, and the ligands AREG, HB-EGF, EPI, TGF-α, and EGF was measured by quantitative polymerase chain reaction in tumor samples from 100 NSCLC patients without EGFR activating mutations. Results were dichotomized into high or low levels of target expression. Coexpression of the ligands and receptors was observed, and a score was developed based on the summed effect of receptors and ligands. Akaike’s information criteria selected the optimal score. Results were correlated with age, sex, stage, histology, performance status, and overall survival. RESULTS: Patients were randomly split 1:1 to create test and validation cohorts. In multivariate analyses, the only individual prognostic marker was EPI (hazard ratio [HR] 0.38 [0.20-0.72], P = .003). The optimal score in the test cohort was validated as a marker of inferior survival in the validation cohort and by bootstrapping. Multivariate analysis confirmed the combined score as a prognostic marker of inferior survival (HR 3.75 [2.17-6.47], P < .00001). CONCLUSION: Our study has developed a model that takes the complexity of the EGF system into account and shows that this model is a strong prognostic marker in NSCLC patients.Despite advances in the treatment, non–small cell lung cancer (NSCLC) remains the leading cause of cancer-related death in the world [1]. In particular, the overall prognosis is poor for the metastatic stages, with a median overall survival (OS) of only 8 to 10 months. Even in the early nonmetastatic stages, the 5-year survival rate is as low as 50% [2], [3]. Prognostic markers are needed to stratify patients with different risk outcome. Several biomarkers have been evaluated in NSCLC, but only a few have proven to be clinically relevant. An activating mutation in the epidermal growth factor receptor (EGFR) is both a well-described predictive marker of benefit of EGFR-targeted tyrosine kinase inhibitors but also a debated prognostic marker of better OS [4], [5], [6], [7], [8], [9]. As EGFR expression has been associated with OS in head and neck, colorectal, and esophagus cancer [10], [11], [12], attention has been directed toward the use of EGFR expression as a prognostic marker in NSCLC, but contradicting results have been demonstrated [13], [14], [15], [16]. The EGF system is complex, and the effect of ligand-receptor interaction depends on a variety of different factors, which provides a plausible explanation for the divergence observed between studies that only evaluate EGFR expression in general. EGFR is one out of four related receptors from the EGF system and is capable of forming homodimers or heterodimers with one of the three other receptors when activated by a ligand. Several ligands from the EGF system such as amphiregulin (AREG), epidermal growth factor (EGF), and transforming growth factor–α (TGF-α) only activate EGFR, whereas some have the ability to activate several combinations of the four EGF receptors like heparin-binding epidermal growth factor (HB-EGF), epiregulin (EPI), and betacellulin (BCL). Most knowledge on the role of the ligands in NSCLC is from in vitro studies or from smaller clinical studies. In vitro studies have suggested that the biological effect of EGFR activation is dependent on the specific activating ligand as well as the dimerization partner [17]. Yet, no clinical studies have evaluated the effect of the network of receptors and ligands influencing EGFR in NSCLC. Furthermore, the majority of the clinical studies exploring EGFR expression are based on immunohistochemistry which is a semiquantitative method with a great risk of interobserver variability. Quantitative gene expression analyses provide a more accurate measure and are therefore more suitable for studies comparing expression levels. Prospectively, we have collected fresh tumor samples from patients suspected of lung cancer. Accordingly, the aim of this study is to evaluate the gene expression of the network of receptors and ligands of the EGF system affecting EGFR as a prognostic markers in NSCLC.     

The Prognostic Role of the Class III β-Tubulin in Non-Small Cell Lung Cancer (NSCLC) Patients Receiving the Taxane/Vinorebine-Based Chemotherapy: A Meta-Analysis

Background

A number of studies have examined the relationship between the expression of the class III β-tubulin (TUBB3) and the treatment responses to the taxane/vinorebine-based chemotherapy in patients with non-small cell lung cancer (NSCLC). However, the results of these studies were inconsistent and inconclusive. Therefore, we conducted an up-to-date meta-analysis to evaluate the prognostic role of TUBB3 in the taxane/vinorebine-based chemotherapy.

Methods

A literature search for relevant studies was conducted in PubMed, Embase, and CNKI. The inclusion criteria were the taxane/vinorebine-based chemotherapy in patients with NSCLC and the evaluation of the clinical outcomes in relation to the expression of TUBB3. The clinical outcomes analyzed in this study included the overall response rate (ORR), overall survival (OS), and event-free survival (EFS). Odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI) were calculated to assess the risk associated with the TUBB3 expression in the taxane/vinorebine-based chemotherapy.

Results

A total of 28 studies with 2401 NSCLC patients were qualified for this meta-analysis. We found that the positive or high level of TUBB3 expression was associated with a poorer ORR (OR = 0.24, 95% CI = 0.16–0.36, p<0.001), an unfavorable OS (HR = 1.52, 95% CI = 1.27–1.82, p<0.001), and a worse EFS (HR = 1.47, 95% CI = 1.24–1.74, p<0.001) compared to the negative or low level of TUBB3 expression. The statistically significant associations between TUBB3 and chemotherapy responses were also observed in the stratified subgroup analysis, which included the analysis by ethnic subgroup (Asian and Caucasian), chemotherapy regimen (taxane-based and vinorebine-based), TUBB3 detection method (IHC and PCR), and treatment strategy (surgery plus adjuvant chemotherapy and palliative chemotherapy).

Conclusions

The expression level of TUBB3 may be a useful biomarker to predict the clinical outcomes of the taxane/vinorebine-based chemotherapy in patients with NSCLC.     

The Pulmonary Fibrosis Associated MUC5B Promoter Polymorphism Is Prognostic of the Overall Survival in Patients with Non–Small Cell Lung Cancer (NSCLC) Receiving Definitive Radiotherapy

BACKGROUND: MUC5B is glycoprotein secreted by bronchial glands. A promoter variant in MUC5B, rs35705950, was previously found to be strongly associated with the incidence of idiopathic pulmonary fibrosis (IPF) and also the overall survival (OS) of such patients. Patients with IPF and patients with radiation pneumonitis (RP) have the similar pathologic process and clinical symptoms. However, the role of rs35705950 in patients receiving thoracic radiotherapy remains unclear. PATIENTS AND METHODS: In total, 664 patients with NSCLC receiving definitive radiotherapy (total dose ≥60 Gy) were included in our study. RP was scored via the Common Terminology Criteria for Adverse Events v3.0. OS was the second end point. MUC5B rs35705950 was genotyped, and Kaplan-Meier and Cox regression analyses were used to evaluate associations between MUC5B rs35705950 and the risk of RP or OS. RESULTS: The median patient age was 66 years (range 35-88); most (488 [73.2%]) had stage III of the disease. Until the last follow-up, 250 patients developed grade ≥ 2 RP, 82 patients developed grade ≥ 3 RP, and 440 patients died. The median mean lung dose was 17.9 Gy (range 0.15-32.74). No statistically significant associations were observed between genotypes of MUC5B rs35705950 and the incidence of RP ≥ grade 2 either in univariate analysis (hazard ratio [HR] 1.009, 95% confidence interval [CI] 0.728-1.399, P = .958) or in multivariate analysis (HR 0.921, 95% CI 0.645-1.315, P = .65). Similar results were also observed for RP ≥ grade 3, while TT/GT genotypes in MUC5B were significantly associated with poor OS in both univariate analysis (HR 1.287, 95% CI 1.009-1.640, P = .042) and multivariate analysis (HR 1.561, 95% CI 1.193-2.042, P = .001). CONCLUSION: MUC5B promoter polymorphism could be prognostic of the OS among NSCLC patients receiving definitive radiotherapy, although no significant associations were found with the risk of RP.     

Trends in Breast Cancer Stage and Mortality in Michigan (1992–2009) by Race,Socioeconomic Status,and Area Healthcare Resources

The long-term effect of socioeconomic status (SES) and healthcare resources availability (HCA) on breast cancer stage of presentation and mortality rates among patients in Michigan is unclear. Using data from the Michigan Department of Community Health (MDCH) between 1992 and 2009, we calculated annual proportions of late-stage diagnosis and age-adjusted breast cancer mortality rates by race and zip code in Michigan. SES and HCA were defined at the zip-code level. Joinpoint regression was used to compare the Average Annual Percent Change (AAPC) in the median zip-code level percent late stage diagnosis and mortality rate for blacks and whites and for each level of SES and HCA. Between 1992 and 2009, the proportion of late stage diagnosis increased among white women [AAPC = 1.0 (0.4, 1.6)], but was statistically unchanged among black women [AAPC = −0.5 (−1.9, 0.8)]. The breast cancer mortality rate declined among whites [AAPC = −1.3% (−1.8,−0.8)], but remained statistically unchanged among blacks [AAPC = −0.3% (−0.3, 1.0)]. In all SES and HCA area types, disparities in percent late stage between blacks and whites appeared to narrow over time, while the differences in breast cancer mortality rates between blacks and whites appeared to increase over time.     

Characterization of AKR4C15, a Novel Member of Aldo–Keto Reductase,in Comparison with Other Rice AKR(s)

Environmental stresses often cause a rapid and excessive accumulation of reactive oxygen species (ROS), the toxicity of which is further amplified by downstream aldehyde production. Aldo–keto reductase (AKR) is a group of enzymes metabolizing aldehyde/ketone to the corresponding alcohol using NADPH as the cofactor. In this study, OsI_20197 (AKR4C15), a novel member of AKR4 subfamily C, was isolated and biochemically characterized. Kinetic studies on bacterially-expressed recombinant AKR4C15 revealed that the enzyme was capable of metabolizing a wide variety of aldehydes but clearly exhibited a preference for three carbon compounds, i.e. methylglyoxal, malondialdehyde and glyceraldehyde. In comparison with His-tagged proteins of AKR4C9 from Arabidopsis and several other rice AKR(s): OsI_04426, OsI_04428, OsI_04429, and OsI_15387, AKR4C15 was the one capable of most efficiently metabolizing MDA and had the highest value of catalytic efficiency, which was higher than the value of AKR4C9, approximately, by 30-fold; while its capability of metabolizing MG was on par with AKR4C9, OsI_04426 and OsI_04428 (AKR4C14); and was considerably higher than the activity of OsI_04429 and OsI_15387. In vivo research on transgenic Arabidopsis seedlings ectopically-expressing AKR4C15 showed that the levels of both MDA and MG were also significantly lower than the levels in wild-type seedlings under both normal and stress conditions, emphasizing the role of AKR4C15 in MG and MDA metabolism. In conclusion, AKR4C15, together with OsI_04426 and AKR4C14, may play protective roles against small reactive aldehydes and medium-chain aldehydes.     

The KCNH2 Genetic Polymorphism (1956, C>T) Is a Novel Biomarker That Is Associated with CCB and α,β-ADR Blocker Response in EH Patients in China

Background

KCNH2 (hERG) potassium channels have an integral role in regulating the excitability of smooth muscle cells. Some pathways driven by angiotensin II, nitric oxide and adrenergic receptors blocker are involved in modulating the properties of KCNH2 potassium channels. And these pathways are closely related to blood pressure regulation. Therefore, we hypothesized that KCNH2 genetic polymorphisms may affect blood pressure response to the antihypertensive drug therapies.

Materials and Methods

To evaluate the interactions between KCNH2 genetic polymorphisms and individual blood pressure response to antihypertensive drugs, 370 subjects with essential hypertension (EH) were studied. In evaluating the interactions between KCNH2 genetic polymorphisms and drug response to blood pressure, multivariable ANOVA analysis followed by Bonferroni correction were carried out.

Results

There were statistically significant interactions between KCNH2 (1956, C>T) polymorphism and DBP change (P = 0.010), MAP change (P = 0.014) on azelnidipine or nitrendipine therapy patients at the end of 6 weeks. We found that the KCNH2 (1956,C>T) polymorphism was associated with the hypotensive effects of α,β-ADR blockers of DBP change at the end of 4 and 6 weeks'' treatment in an age- and gender-dependent manner (P = 0.007 and 0.019, respectively). Similar results were also observed for changes in MAP at the end of 4 and 6 weeks (P-values were 0.035 and 0.078, respectively). While patients who received imidapril, candesartan and irbesartan therapy, no significant difference in drug response among KCNH2(1956,C>T) genotype was observed.

Conclusion

We have reported for the first time that KCNH2 (1956, C>T) polymorphism is associated with efficacy of antihypertensive drugs CCBs and ADR blockers, and may serve as a novel biomarker for individualized therapy for certain antihypertensive drugs.     

Prostate Health Index (Phi) and Prostate Cancer Antigen 3 (PCA3) Significantly Improve Prostate Cancer Detection at Initial Biopsy in a Total PSA Range of 2–10 ng/ml

Many efforts to reduce prostate specific antigen (PSA) overdiagnosis and overtreatment have been made. To this aim, Prostate Health Index (Phi) and Prostate Cancer Antigen 3 (PCA3) have been proposed as new more specific biomarkers. We evaluated the ability of phi and PCA3 to identify prostate cancer (PCa) at initial prostate biopsy in men with total PSA range of 2–10 ng/ml. The performance of phi and PCA3 were evaluated in 300 patients undergoing first prostate biopsy. ROC curve analyses tested the accuracy (AUC) of phi and PCA3 in predicting PCa. Decision curve analyses (DCA) were used to compare the clinical benefit of the two biomarkers. We found that the AUC value of phi (0.77) was comparable to those of %p2PSA (0.76) and PCA3 (0.73) with no significant differences in pairwise comparison (%p2PSA vs phi p = 0.673, %p2PSA vs. PCA3 p = 0.417 and phi vs. PCA3 p = 0.247). These three biomarkers significantly outperformed fPSA (AUC = 0.60), % fPSA (AUC = 0.62) and p2PSA (AUC = 0.63). At DCA, phi and PCA3 exhibited a very close net benefit profile until the threshold probability of 25%, then phi index showed higher net benefit than PCA3. Multivariable analysis showed that the addition of phi and PCA3 to the base multivariable model (age, PSA, %fPSA, DRE, prostate volume) increased predictive accuracy, whereas no model improved single biomarker performance. Finally we showed that subjects with active surveillance (AS) compatible cancer had significantly lower phi and PCA3 values (p<0.001 and p = 0.01, respectively). In conclusion, both phi and PCA3 comparably increase the accuracy in predicting the presence of PCa in total PSA range 2–10 ng/ml at initial biopsy, outperforming currently used %fPSA.     

Comparison of Clinicopathological Features and Treatments between Young (≤40 Years) and Older (>40 Years) Female Breast Cancer Patients in West China: A Retrospective,Epidemiological, Multicenter,Case Only Study

The incidence of young cases of breast cancer is higher in China compared to the western world. We aimed to explore differences in risk factors, clinicopathological features and treatment modes of young female breast cancer compared to older patients in West China. We collected clinical information from 12,209 female breast cancer patients in West China, including risk factors, clinicopathological features and treatment modes, from January 2010 to December 2012. Chi-square tests and the multivariate logistic regression analysis were applied for statistical analysis. There were 2,682 young (≤40 years) cases and 9,527 older cases at the time of breast cancer diagnosis. Young patients had a greater tumor diameter at diagnosis, and a higher probability of axillary lymph node and distant metastasis (P < 0.05). The progesterone receptor positive expression rate, estrogen receptor/progesterone receptor double positive expression rate, and human epidermal growth factor receptor 2 (HER2) negative expression rate was higher in young patients compared to older patients (P < 0.05). For young patients, the age at menarche was earlier, they had lower marriage rates, fewer pregnancies and births, and a lower breastfeeding rate (P < 0.05). A higher proportion of young patients underwent advanced operations, neoadjuvant and adjuvant chemotherapy, radiotherapy, and endocrine therapy compared to older patients (P < 0.05). We found significant differences in the clinicopathological features, risk factors and treatment modes between young (≤40 years) and older (>40 years) female breast cancer patients in West China. As some of these results differ from those found in the western female population, it is likely that the mechanism of tumorigenesis of young female breast cancer patients in West China may differ from that in western developed countries. Further investigation into the regional differences in breast cancer tumorigenesis is warranted.     

Dose Responsiveness and Variation Among Inbred Strains of Mice in Production of Interferon After Treatment with Poly (I)· Poly (C) [Poly-d-Lysine] Complexes

Poly-d-lysine forms a stochiometric complex with poly(I) . poly(C) which has a higher T(m) (83 C in 0.15 m NaCl) than the uncomplexed double-stranded polyribo-nucleotide (63 C). The complex was superior to poly(I) . poly(C) alone as an interferon inducer in vivo. Significant serum interferon titers were attained in Swiss mice during a 24-hr period after intraperitoneal injection of 10 to 300 mug of poly(I) . poly(C) [1.0 poly-d-lysine] complex, at concentrations of 100 to 1,000 mug/ml. The serum interferon responses (average and maximum titers) of a series of inbred strains of mice to a single intraperitoneal injection of 100 mug of complex decreased in the order: Swiss > DBA/2 > C3H > BALB/c > CF-1 > AKR, C57Bl/6, NZB > SJL > NZW and varied by a factor of approximately 100 from the most to the least responsive.     

The role of rock-phosphate-solubilizing fungi and vesicular–arbusular-mycorrhiza (VAM) in growth of wheat plants fertilized with rock phosphate

A total of 36 fungal species isolated from soil were tested for their ability to solubilize rock phosphate (RP) in agar plates. Most of these fungi were non-rock phosphate solubilizers, but two isolates, Aspergillus niger and Penicillium citrinum, had high activity. Liquid culture experiments revealed that both fungi caused a remarkable drop in pH of culture media and solubilized considerable amounts of phosphate. The effects on wheat of inoculation with vesicular–arbuscular mycorrhizal fungi and rock-phosphate-solubilizing fungi and fertilization with rock phosphate were studied in sterilized pot soils, nonsterilized pot trials and in field plot soils. Rock phosphate fertilization and inoculation with Glomus constrictum and rock-phosphate-solubilizing fungi (A. niger and P. citrinum) significantly increased dry matter yield of wheat plants under all experimental conditions. However, the effect was more evident in non- sterilized pot soils and in the field than in sterilized pots. Rock phosphate had no significant effect on the total phosphorus content of plants grown under pot conditions but it was significantly increased in field plots; the effect of inoculation with fungi (G. constrictum, A. niger and P. citrinum) on plant phosphorus was closely related to this in dry matter production. The greatest positive effect on growth and phosphorus contents of wheat plants was recorded in the treatments that received rock phosphate and were inoculated with a mixed inoculum of the three microorganisms used, followed by dual inoculation treatments of G. constrictum plus either A. niger or P. citrinum.     

Use of Complementary and Alternative Medicine (CAM) as Part of the Oncological Treatment: Survey about Patients’ Attitude towards CAM in a University-Based Oncology Center in Germany

IntroductionTo understand if and which patients would be open-minded to Complementary and Alternative Medicine (CAM) use parallel to their oncological treatment. Moreover, we sought to determine which methods are most accepted and which are the primary motivators to use CAM.MethodsWe developed and anonymously conducted a questionnaire for patients in the oncology center (TU Munich). Questions focus on different CAM methods, previous experiences, and willingness to apply or use CAM when offered in a university-based setting.ResultsA total of 171 of 376 patients (37.4% women, 62.0% men, 0.6% unknown) participated. This corresponds to a return rate of 45%. Median age was 64 years (17–87 years). Of all participants, 15.2% used CAM during their oncological therapy; 32.7% have used it in the past. The majority (81.9%) was not using CAM during therapy; 55.5% have not used CAM in the past respectively. The analysis revealed a significant correlation between education and CAM use during therapy (r = 0.18; p = 0.02), and CAM use in the past (r = 0.17; p = 0.04). Of all patients using CAM during therapy, favored methods were food supplements (42.3%), vitamins/minerals (42.3%), massage (34.6%). Motivations are especially the reduction of side effect and stress, the positive effect of certain CAM-treatments on the immune system and tumor therapy. Results showed no difference between women and men. Most patients not having had any experience with CAM complain about the deficiency of information by their treating oncologist (31.4%) as well as missing treatment possibilities (54.3%).ConclusionSince many patients believe in study results demonstrating the efficacy of CAM, it stresses our task to develop innovative study protocols to investigate the outcomes of certain CAM on symptom reduction or other endpoints. Thus, prospective trials and innovative evidence-based treatment concepts to include CAM into high-end oncology is what patients demand and what a modern oncology center should offer.     

Turbidity,nutrients and phytoplankton primary production in the Oosterschelde (The Netherlands) before,during and after a large-scale coastal engineering project (1980–1990)

Turbidity, nutrient concentrations and phytoplankton primary production were monitored in the Oosterschelde before, during and after the construction of a storm-surge barrier and two compartment dams.Flow velocities and suspended matter concentrations decreased severely, causing an increased transparency of the watercolumn. In the eastern and northern compartments, the previously pronounced seasonal variation disappeared.Reduction of the freshwater load and decreasing nutrient concentrations in the adjacent North Sea coastal waters resulted in lower nitrite + nitrate and silicate concentrations. Autumn phosphate concentrations remained at the same level as before the nutrient reduction. Silicate was a limiting nutrient during the pre-barrier period and nitrogen and silicate were limiting during the post-barrier period.Annual patterns in chlorophyll-a concentrations in the western and central compartments showed no obvious trend; in the eastern and northern compartments higher values were measured from 1985 onwards.Primary production during the period 1980–1990 varied between 176 and 550 g C m^–2 yr^–1. The annual primary production in the western compartment had decreased, while in the central and eastern compartments annual primary production did not change: the formerly existing gradient disappeared. In the northern compartment higher chlorophyll-a concentrations and high annual production suggest that the phytoplankton could benefit from the increased transparency while nutrient concentrations were still high enough to support phytoplankton growth.Changes in photosynthetic physiological parameters were observed which suggested shade adaptation. This is in contrast to improved light conditions and reduced nutrient availability. The apparent incoherence with light-shade adaptation theory may be explained by the species shift that occurred.As a result of the opposite effects of a more favourable light climate and a reduced nutrient availability, together with the resulting species shift, the annual primary production showed a large degree of homeostasis.     

Nutrient and plant dynamics in Lake Agmon Wetlands (Hula Valley,Israel): a review with emphasis on Typha domingensis (1994–1999)

Shallow lake Agmon is a newly created subtropical wetland in north-eastern Israel. The lake is part of the Hula Project aimed at slowing down deterioration processes of the peat soils, to establish infrastructure for ecotourism as an income for the land owners, and nutrient removal from Lake Kinneret inputs. An onset of benthic filamentous macro-green algae during late winter–spring season, followed by submerged macrophytes vegetation during spring–summer was documented. The phosphorus summer loads are mostly plant–mediated internal fluxes and nitrogen intensively removed from lake waters by sedimentation and denitrification. The summer phytoplankton, mostly colonial cyanobacteria, are P limited. During 1995 and early 1996, dense Typha domingensisstands were developed in the southern half of the Lake (chalk-marl bottom sediments). The P-limited Typhavegetation collapsed within less than half a year and reappeared in the south-eastern part of the lake where sediments were exposed and oxidized. It is hypothesized that phosphorus cycle is a strong dependant of macrophyte mediation, and P deficiency in the sediments predominantly affected Typhadecline and an increase of P availability later enabled the reappearance of the Typhastands.     

Feasibility of Elective Nodal Irradiation (ENI) and Involved Field Irradiation (IFI) in Radiotherapy for the Elderly Patients (Aged ≥ 70 Years) with Esophageal Squamous Cell Cancer: A Retrospective Analysis from a Single Institute

PurposeWe conducted a retrospective analysis to assess the feasibility of involved field irradiation (IFI) in elderly patients with esophageal squamous cell cancer (ESCC).ResultsA total of 137 patients were enrolled. Fifty-four patients (39.4%) were allocated to the ENI group and 83 patients (60.6%) to the IFI group, the median doses in the two groups were 60 Gy and 59.4 Gy, respectively. For the entire group, the median survival time (MST) and PFS were 16 months and 12 months, respectively. The median PFS and 3-year PFS rate in the ENI group were 13 months and 20.6%, compared to 11 months and 21.0% in the IFI groups (p = 0.61). The MST and 3-year OS rate in the ENI and IFI groups were 17 months and 26.4% and 15.5 months and 21.7%, respectively (p = 0.25). The rate of grade ≥ 3 acute irradiation esophagitis in the ENI group was significantly higher than that in the IFI group (18.5% vs. 6.0%; p = 0.027). Other grade ≥ 3 treatment-related toxicities did not significantly differ between the two groups.ConclusionsIFI resulted in decreased irradiation toxicities without sacrificing OS in elderly patients with ESCC.